The overall goal of my group is to develop advanced magnetic resonance spectroscopy and imaging techniques and to apply them and other complementary methods to studying brain metabolism and neurotransmission in both human subjects and in animal models. Magnetic resonance spectroscopy, in principle, allows measurement of neurotransmitters glutamate and GABA, which play important roles in many psychiatric diseases including depression and schizophrenia, and their metabolism. During 2005-2006, significant progress was made in the development of new spectroscopic techniques for single-voxel glutamate and GABA measurement. In particular, we have developed a method which allows measuring the dynamic turnover of 13C-labeled isotopomers of glutamate and glutamine. (S Xu, and J Shen, In vivo dynamic turnover of cerebral 13C isotopomers from [U-13C]glucose, J Magn Reson, 182:221-228 (2006)). A lag in transition of glutamine C4 pattern from doublet dominance to quartet dominance as compared to that of glutamate was found, which provides verification of a significant intercompartmental glutamate-glutamine cycling flux. Proton editing of glutamate is being perfected. We have measured a significant increase in oxygen consumption during focal activation of brain (J Yang, and J Shen, Increased oxygen consumption in the somatosensory cortex of alpha-chloralose anesthetized rats during forepaw stimulation determined using MRS at 11.7 Tesla, NeuroImage, 32:1317-1325 (2006)). We have applied GABA editing techniques to characterization of alterations of GABA in depressed patients (G Hasler, JW van der Veen, T Tumonis, N Meyers, J Shen, and WC Drevets, Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined by proton magnetic resonance spectroscopy, Arch Gen Psychiatry, in press.) and to determination of gray and white matter differences in GABA concentration in healthy subjects (I-Y Choi, S-P Lee, H Merkle, and J Shen, In vivo detection of gray and white matter differences in GABA concentration in the human brain, NeuroImage, 2006 Aug 1; [Epub ahead of print]). The GABA-glutamine neurotransmitter cycling flux has also been quantified in vivo by us (J Yang, SS Li, J Bacher, and J Shen, Quantification of cortical GABA-glutamine cycling rate using in vivo magnetic resonance signal of [2-13C]GABA derived from glia-specific substrate [2-13C]acetate, Neurochem Intl., in press.). To implement in vivo 13C MRS for human studies, we have devised a novel strategy using [2-13C]glucose and detecting the kinetics of 13C label incorporation into the carboxylic acid spectral region (S Li, J Yang, and J Shen, A novel strategy for in vivo cerebral 13C MRS using very low RF power for proton decoupling, Magn Reson Med., revised.) This strategy dramatically reduces RF power deposition into the brain required for proton decoupling, therefore, overcoming the major technical hurdle preventing wide application of in vivo 13C MRS. This work is to received a "Certificate of Merit Award" by the European Society for Magnetic Resonance in Medicine and Biology in September, 2006. In addition, we continue to develop our recently discovered 13C magnetization transfer effect for in vivo enzymology studies. Our latest achievements in this area include detection and quantification of the lactate dehydrogenase (S Xu, J Yang, and J Shen, In vivo 13C saturation transfer effect of lactate dehydrogenase reaction, Magn Reson Med., revised) and malate dehydrogenase reaction J Yang, and J Shen, Relayed 13C magnetization transfer. Detection of malate dehydrogenase reaction in vivo, submitted to J Magn Reson.) in the brain in vivo